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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 14 MAR 1977 to 17 MAR 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets important criteria of today standard methods even though not examined until full reversibility of effects seen.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report date:
1977

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: FDA guideline (Federal Register Vol. 38, nr. 187, p. 27019, 1973)
Deviations:
no
Principles of method if other than guideline:
Pigment Orange 36
GLP compliance:
no
Remarks:
study was performed previous to GLP implementation

Test material

Constituent 1
Chemical structure
Reference substance name:
2-[(4-chloro-2-nitrophenyl)azo]-N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-oxobutyramide
EC Number:
235-462-4
EC Name:
2-[(4-chloro-2-nitrophenyl)azo]-N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-oxobutyramide
Cas Number:
12236-62-3
Molecular formula:
C17H13ClN6O5
IUPAC Name:
2-[(4-chloro-2-nitrophenyl)diazenyl]-3-oxo-N-(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)butanamide
Test material form:
solid: bulk

Test animals / tissue source

Species:
rabbit
Strain:
other: New Zealand
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Housing: single
- Diet: ERKA 8300 (Futtermittelwerke Robert Koch oHG, Hamm, Germany), ad libitum
- Water: ad libitum

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
Duration of treatment / exposure:
24 h after exposure eyes were washed with physiological saline.
Observation period (in vivo):
72 h with observation time points at 1, 7, 24, 48 and 72 h after application.
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 h

SCORING SYSTEM: according to Draize Scale.

TOOL USED TO ASSESS SCORE: loupe / fluorescein (at 48 and 72 h reading)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not relevant since no effect
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not relevant since no effect
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: #1 and #5 each
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not relevant since no effect
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: #2 and #3 each
Time point:
other: mean of 24, 48 and 72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #4
Time point:
other: mean of 24, 48 and 72 h
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: The effect was slight and fully reversible in the remaining animals within the observation period of 72 h. Therefore full reversibility was expected in animal #4 within 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not relevant since no effect
Irritant / corrosive response data:
Individual animal data for animal #1/#2/#3/#4/#5/#6 at time point 1, 7, 24, 48 and 72 h.
cornea score: all scores 0
iris score: all scores 0
conjunctivae redness: 1/1/1/1/1/1, 1/1/1/1/1/1, 0/1/1/1/0/1, 0/1/1/1/0/0, 0/0/0/1/0/0
chemosis: 1/1/1/1/1/0, 2/1/1/1/2/2, 0/0/0/0/0/0, 0/0/0/0/0/0, 0/0/0/0/0/0
Other effects:
No other effects reported

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Regulation (EC) no 1272/2008
Conclusions:
The test material is very slightly irritating to the eyes under the test conditions which are basically in accordance with todays standard methods regarding dosing, exposure duration, scoring system and reading time points. 4/6 animals showed a conjunctiva redness score of one 24 h after removal of the test item, the effect being fully reversible within 72 h for all animals except one. No other effects were observed.
The slight effect does not result in a classification of the test item according to the classification criteria of Regulation (EC) No 1272/2008.
Executive summary:

Test material was subject to a test of eye irritancy according to FDA guidelines (Fed. Reg. Vol. 38, No. 187, p. 27019, 1973). 100 mg of substance were applied to one eye of six animals. The eyes were washed 24 h after application and eye responses were noted for 72 h after start of the exposure. Only slight effects could be observed (conjunctiva redness score of 1 in 4/6 animals after 24 h, which was fully reversible within 72 h at all animals except one). No other effects could be observed in any animal. Overall effects observed are minimal and it is anticipated that this slight conjunctival effect which remained until 72 hours in one animal might be reversible within a prolonged observation period.